AUCTORES
Globalize your Research
Case Report | DOI: https://doi.org/10.31579/2690-4861/143
*Corresponding Author: Deniz Karakaya, Department of Pediatric Emergency Department, Ankara University Medical School, Ankara, Turkey.
Citation: D Karakaya, O Perk, S Özhan, D Tekin, T Kendirli. (2021) Treatment of Pediatric Life Threatening Amitriptilin Intoxication with Plasma Exchange. International Journal of Clinical Case Reports and Reviews. 8(1); DOI:10.31579/2690-4861/143
Copyright: © 2021 Deniz Karakaya, This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received: 07 June 2021 | Accepted: 02 August 2021 | Published: 11 August 2021
Keywords: amitriptyline; plasma exchange; intoxication; pediatric
Tricyclic antidepressant (TCA) overdose is one of the most common causes of serious drug poisoning in children. Amitriptyline is a major TCA drug that is used widely. Tricyclic antidepressant intoxications are very important because of their severe adverse effects and probable fatal outcomes. It may cause cardiovascular, respiratory and neurological side effects. Poisoning results in hypotension, cardiac dysrhythmia, depression of the central nervous system (CNS) and seizures. The most common effects on the central nervous system are agitation, lethargy, seizures, and coma. Cardiovascular toxicities manifest itself especially with electrocardiographic (ECG) abnormalities, arrhythmias, and refractory hypotension and they are the leading cause of fatal outcome.
Treatments in TCA overdose are mainly conservative including gastric lavage, activated charcoal and vasopressors for hypotension, sodium bicarbonate for dysrhythmias, and benzodiazepines for seizures. Magnesium sulfate (MgSO4) also has an effective role in the treatment of fatal cardiac arrhythmias occurring in high-dose amitriptyline intoxication. Intravenous lipid emulsions have been increasingly studied as antidotes to reverse acute, life-threatening drug toxicity. Unpredictable and poor results with hemoperfusion (HP) and hemodialysis (HD) should be expected, as the drug binds rapidly to tissues and has a large volume of distribution. But beside it, in the last few years, HP has been successfully used in severe TCA overdose, especially in patients with persistent respiratory, cardiac, and neurologic symptoms. Besides all these, recently, plasma exchange, have been increasingly used. A reduction of plasma levels by 63% after plasmapheresis in TCA poisoning has been reported. Here, we report a successful treatment of plasma exchange 3 year patient with amitriptyline overdose who had arrhythmias and seizures that wasn't respond all to conservative therapies.
Tricyclic antidepressant (TCA) overdose is one of the most common causes of serious drug poisoning in children. Amitriptyline is a major TCA drug that is used widely. Tricyclic antidepressant intoxications are very important because of their severe adverse effects and probable fatal outcomes. It may cause cardiovascular, respiratory and neurological side effects. Poisoning results in hypotension, cardiac dysrhythmia, depression of the central nervous system (CNS) and seizures [1]. The most common effects on the central nervous system are agitation, lethargy, seizures, and coma. Cardiovascular toxicities manifest itself especially with electrocardiographic (ECG) abnormalities, arrhythmias, and refractory hypotension and they are the leading cause of fatal outcome [2].
Treatments in TCA overdose are mainly conservative including gastric lavage, activated charcoal and vasopressors for hypotension, sodium bicarbonate for dysrhythmias, and benzodiazepines for seizures [1]. Magnesium sulfate (MgSO4) also has an effective role in the treatment of fatal cardiac arrhythmias occurring in high-dose amitriptyline intoxication [3, 4]. Intravenous lipid emulsions have been increasingly studied as antidotes to reverse acute, life-threatening drug toxicity [5, 6]. Unpredictable and poor results with hemoperfusion (HP) and HD should be expected, as the drug binds rapidly to tissues and has a large volume of distribution [7, 8, 9]. But beside it, in the last few years, HP has been successfully used in severe TCA overdose, especially in patients with persistent respiratory, cardiac, and neurologic symptoms [10, 11]. Besides all these, recently, plasma exchange [12, 13], have been increasingly used. Plasma exchange is the removal of the patient's plasma and replacement with another fluid. A reduction of plasma levels by 63
A 3, 5-year-old girl was brought with 112 ambulance complaints of wheezing, bruising, blurring of consciousness and seizures. We learned that the patient slept at 22:00 in the evening and she woke up at 3:00 in the morning when the family noticed the wheezing breath of the patient. When the parents notice her, she was cyanotic, the respiration was irregular and the consciousness was closed. She delivered to our unit by 112 emergency servise. A brief (5-10 sc) generalized tonic clonic seizure was observed 3 times during the transfer of the patient. The patient's resume and family trait did not have a feature.
On physical examination, heart rate was 110 / min, respiration rate 32/min ,blood pressure 110/60 mm Hg SPO2: 99% temperature: 36.1 C and blood sugar: 118 mg / dL. Overall status: Poor Neurological: Consciousness and her response to painful stimulus was minimal DTR: normoactive IR: Bilateral weak and MI: assessed as absent. Respiratory irregularities and coarse secretary breath sounds were present. Other system examinations were natural. Total blood count: normal, the electrolyte levels, liver and kidney function tests were normal. Acute phase reactants negative, blood gas was pH: 7.27 pCO2: 32 lac: 1.7 hCO3: 15.5 coHB: 0.8.
The patient was monitorized. Intravenous route opened. She was initially given 20 ml/kg isotonic solution for circulatory support. Her respiration was stable and effective so she was not intubated at that time. Short seizures and consciousness blurring were assessed as continuing patient status. The patient was given IV diazepam two times. Intravenosus eptantoin and iv levatiracetam were loaded. The patient's convulsions stopped but the consciousness was closed. The story of the patient, who was completely healthy before, was repeated. Her relatives didn’t estimated that she had taken medicine or travma. Computed tomography was normal. There was no height of fever. There was no epilepsy story in the family. The patient was interrogated for drug intake again. The family said they saw a medication box in the hands of the patient at noon the day before, but did not know what the medicine was. We wanted to bring the medicine box from the family. At that time, extrasystoles were identified on the monitor. Learned that the drug is laroxyl (amitriptyline) and the treatment and follow-up of the patient was approached as TCA intoxication. The patient weight was 15 kg. It was estimated that she took approximately 35 mg/kg of amitriptyline about 18 hours before admission. A sodium bicarbonate IV bolus was administered for the patient's extrasystoles. The patient was observed to return to sinus rhythm for a short time. For this reason, NaHCO3 was repeated 5 times and followed by continuous IV infusion for treatment of cardiac arrhythmias and for alkalinization. Patient received intensive care. Lidocaine therapy for arrhythmia was started. Because the patient’s clinical condition did not improve, hemoperfusion was considered. Plasma Exchange was done. On the follow-up, the patient's consciousness was opened, the arrhythmia was strained, the seizure did not recur. Support treatments were cut off. On the second day of admission, the patient did not need intensive care and was discharged after 24 hours of more observation.
Amitriptyline is registered as a tricyclic antidepressant (TCA). It is also being used off label for additional purposes, such as neuropathic pain, tension headache, and posttraumatic stress. Tricyclic antidepressant overdosage has toxic effects over cardiovascular, autonomous nervous, and central nervous systems, and may result in cardiac conduction delays, dysrhythmia, hypotension, altered mental status and seizures [14]. Serious and lethal toxic effects have been reported with TCA intoxications of 10 to 30 mg/kg and 50 mg/kg, respectively [1, 14]. Exact fatal serum levels of amitriptyline in children are not known. Ash et al. reported that the lethal dose can be variable and ingestion of more than 1 g TCA or a blood level of 1,000 mg/l predicts a high risk of mortality [10]. Children are more susceptible to TCA overdose and fatal cases with ingestion of only one capsule or table have been reported [14]. For this reason, estimated amount of drug taken based on anamnesis alone may be misleading.
Conduction delays may become apparent on electrocardiogram as PR and QT prolongation, QRS widening that may resemble right bundle block or Brugada electrocardiographic pattern [15, 16]. Widening of the QRS complex> 100 milliseconds is associated with the development of seizures and arrhythmias. Sinus and supraventricular tachycardia, premature ventricular complexes, idioventricular tachycardia, VT or fibrillation may be seen [1, 14]. The most serious causes of death in TCA intoxication are persistent hypotension. In addition that, possible mechanisms for TCA-induced neurotoxicity include g-aminobutyric acid receptor antagonism, neuronal Na channel blockage and central anticholinergic activity [5].
Recommended treatments in TCA overdose are mainly conservative, including gastric lavage and activated charcoal and bicarbonate infusion to prevent cardiac side effects [17,18]. Inhibition of absorption by gastric lavage should be considered if ingestion was recent (1–2 hours) and activated charcoal can be administered because amitriptyline delays gastric emptying due to its anticholinergic effects. Repeated doses of charcoal may be necessary to interrupt the enterohepatic cycle. In Tricyclic antidepressant intoxication, sodium bicarbonate treatment is suggested as the first agent. Sodium bicarbonate is known to decrease ventricular arrhythmia frequency, prevent QRS prolongation, and correct hypotension. This effect can be accentuated by increasing plasma sodium concentration and alkalinization [14]. A decrease in Na entry into cells decreases the myocardial contractility and leads to hypotension [5]. Increasing plasma sodium concentration may prevent cardiac arrhythmias by decreasing sodium channel inhibition caused by TCA intoxication [1, 6]. Magnesium sulfate is also efficient in treating sustained ventricular arrhythmias, especially ventricular and torsade de pointes tachycardia and is known to prevent sudden deaths. Magnesium infusion is reported to increase intracellular potassium levels more significantly than potassium infusion. Antiarrhythmic and anticonvulsive agents are also used in symptomatic treatment. Benzodiazepine is the first choice for anticonvulsive therapy and phenytoin is contraindicated for TCA-like effects. In the case of antiarrhythmic treatment, lidocaine should be preferred instead of the commonly used amiadorone.
Following oral administration, TCA are absorbed rapidly and peak plasma levels occur within 2–4 h [19]. Tricyclic antidepressant plasma elimination half-life is about 16 h in healthy volunteers ingesting a single therapeutic dose. Ash et al. Tricyclic antidepressants bound to plasma proteins with high affinity [10]. Moreover, these drugs are not dialysable because of their high protein affinity. Frank and Klerdorf reported that HD would only compensate the acid-base and electrolyte status however, there are conflicting reports of the efficacy of HP in TCA poisoning [20]. Similarly, Bayrakc¸i et al. reported successful treatment of severe amitriptyline poisoning in three cases by plasma exchange [21]. After ingestion, TCA are absorbed rapidly and quickly taken up by the tissues, importantly by the lung and the heart [10]. It seems reasonable that HP performed in an early stage of ingestion would be more efficient [8]. In addition to removing free drug in blood, removal of unmeasured metabolite from the blood could also help in clinical improvement [10]. Heath et al. reported that respiratory depression, seizure severe arrhythmias such as ventricular tachycardia or fibrillation, or an increased QRS interval are the criteria for HP use in TCA overdose [7]. There is also an increasing interest in the use of intravenous lipid emulsion therapy to treat life threatening toxicity associated with lipophilic drugs in adults and children. In the 14 pediatric cases we reviewed, 13 patients appeared to have a beneficial response following intravenous lipid emulsion therapy, despite being unresponsive to standard resuscitation methods [22]. Further reporting of pediatric cases will guide the optimal use and safety profile of intravenous lipid emulsion for the emergent treatment of acute drug toxicity [22].
In our case we experienced that, the detailed questioning of the history is very important. Our patient was initially assessed as status. The treatment approach then changed completely. Since our patient was admitted approximately 18 hours after drug ingestion, gastric lavage was not performed. The patient who was conscious off was not given active charcoal. The first drug that we administered to our patient was sodium bicarbonate infusion, but it did not make totally change in the cardiac rhythm. İntravenous lidocain was initiated for arrytmies. We did not record a marked decrease in our patient’s blood pressure. It was either because she did not have hypotension or having been given intravenous isotonic crystalloid solution from the time of admittance. Phenytoin loading was performed for the patient's seizure. Phenytoin was contraindicated in these patients as an antiepileptic agent. This might have triggered arrhythmia. The anticonvulsant treatment plan could change if the etiologic agent was learned earlier. Despite the conservative and symptomatic treatment, our patient continued to have persistent symptoms. Then HP was considered to control the resistant arrytmies and unconsciousness. The arrytmies returned to normal sinus rhythm at the end of HP and his seizures did not recurr. We observed a very good clinical response in our patient and found HP a useful treatment modality in a child with severe amitriptyline intoxication.
Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.
Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.
Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.
Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.
We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.
The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.
Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.
Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.
Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.
Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.
Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.
This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.
Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.
As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.
Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.
International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.
Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.
Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
